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Biomedical Interventions: Microbicides

Microbicides are products formulated for individuals to apply topically (vaginally or rectally) to reduce their risk of HIV and possibly other sexually transmitted infections. At present, this approach is experimental, although several broad-spectrum microbicides have been clinically evaluated. Microbicides comprise a subset of approaches to pre-exposure prophylaxis (PrEP); oral approaches to PrEP are addressed in a separate entry.

II. Epidemiological Justification for the Prevention Area

In generalized epidemics, women are at a disproportionate risk of HIV infection for biological as well as social reasons. Although condoms are highly effective in preventing HIV transmission, it can be difficult for women to negotiate safer sex because the male partner often controls whether a condom is used. Microbicides were initially proposed as a woman-controlled or -initiated prevention method for vaginal application, something a woman could use to protect herself.

The first microbicides studied were broad-spectrum compounds that were expected to inactivate HIV and other microbes by enhancing vaginal pH or by coating cell surfaces, preventing the binding of viruses or the entry of microbes into tissue. None of these approaches proved effective.

However, clinical trial results released in 2010 by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) provided the first proof of concept for microbicide efficacy. This study, CAPRISA 004, found that a topical gel formulation of the antiretroviral drug tenofovir significantly reduced the risk of acquiring HIV and herpes simplex virus 2 (HSV-2) in women who use it regularly around the time of sex. However, in late 2011, the gel arms of another clinical trial evaluating daily use of one percent tenofovir gel were stopped early by the trial's data safety and monitoring board because there was no evidence that the gel was effective in reducing the risk of HIV acquisition. (This trial was also evaluating oral tenofovir and oral Truvada). Further analysis of data from this trial, known as VOICE (Vaginal and Oral Interventions to Control the Epidemic), is needed to explain the discrepancy between the two trial results.

Another trial evaluating vaginal use of one percent tenofovir gel is underway using the same dosing schedule as in CAPRISA 004. This trial, FACTS 001, is being conducted by the Follow-on African Consortium for Tenofovir Studies (FACTS) which expects to have data available in 2014. If FACTS confirms effectiveness of one percent tenofovir gel, additional steps will be needed before it can be licensed and marketed. Two safety and effectiveness trials of a vaginal ring containing dapivirine are scheduled to start in 2012.

Researchers are also evaluating whether these products could be safe and effective when applied rectally, given that anal sex carries an even higher risk of HIV transmission for heterosexuals and men who have sex with men. Developing a rectal microbicide is more challenging because the rectal mucosa is highly susceptible to HIV infection. Also, the colorectal tract has a greater surface area than the vagina, requiring a rectal microbicide to have greater coverage. Trials of a rectal formulation of tenofovir gel are moving forward.

III. Core Programmatic Components

Further studies are needed to confirm the safety and efficacy of tenofovir gel and other products being developed; it will be several years before this or any other microbicide is marketed. In the meantime, policymakers and program directors need to work closely with the community to put this potential prevention tool to best use. The following key activities will be necessary:

Support of research to assess how the microbicide might be accepted and used in the local setting. What impact will it have on sexual risk-taking?

Development of educational materials and campaigns to promote adherence and correct use while helping people understand the potential limitations of products that are only partially effective.

Buildup of a stable supply chain and strategic distribution plan to ensure access to those who need the microbicide.

Ensuring access to regular and routine HIV testing, especially rapid point-of-care HIV tests, to reduce the risk that people who are HIV-positive and are unaware of their HIV status will use the product.

Performing surveillance for adverse events and for detection of any increase in HIV transmission or the possibility of individuals not yet on antiretroviral therapy developing drug resistance.

IV. Current Status of Implementation Experience

While an approved microbicide is not yet available, the clinical trials in Africa and India provide insights into how best to introduce microbicides into communities and fuel hope that women-driven prevention technology might further women's empowerment. For instance, one group in Pune, India, has explored how discussion of microbicides among couples could enhance partner communication about sex.

While the success of the CAPRISA trial is promising, additional work will be necessary to complete the critical next phases of research that could lay the groundwork for large-scale rollout. A number of additional trials over the coming years should deliver further results.

Read these summaries of the research providing the evidence-base that supports the prevention approach

Microbicide Trials Network Statement on Decision to Discontinue Use of Tenofovir Gel in VOICE, a Major HIV Prevention Study in Women

Microbicide Trials Network, November 25, 2011.

The Microbicide Trials Network dropped tenofovir gel from its Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial following a routine Data Safety and Monitoring Board review that concluded that tenofovir gel was not effective in preventing HIV in the women enrolled in the trial. VOICE, an HIV prevention trial, has been evaluating two antiretroviral approaches for preventing the sexual transmission of HIV in women—daily use of one of two different antiretroviral tablets (tenofovir or tenofovir emtricitabine) or of a vaginal gel. The trial has enrolled 5,029 women at 15 sites in Uganda, South Africa, and Zimbabwe, and had earlier discontinued the oral tenofovir. The study found no safety concerns with any of the study products. It is not clear why tenofovir gel did not reduce the risk of HIV acquisition among women in this trial when an earlier trial (CAPRISA 004, which followed a different dosing schedule) showed a reduction in risk. Complete analysis of the trial data will take place after the trial is completed and all of the data are analyzed. The trial team expects results to be available in late 2012 or early 2013.

This is the first clinical trial indicating the effectiveness of a vaginal microbicide in reducing HIV infection in women. Nearly 900 sexually active women aged 18 to 40 in Durban and Vulindlela, South Africa, were randomized to receive tenofovir or placebo within 12 hours before having sex and as soon as possible within 12 hours after having sex. Monthly support meetings with participants highlighted the importance of consistent and correct microbicide use, identified ways to overcome obstacles to use, and set goals for perfect adherence for each month. Despite this, 40 percent of the study participants used the gel for less than 50 percent of sex acts. After 12 and 24 months of follow-up, HIV incidence in the tenofovir arm was 50 percent and 40 percent lower than the placebo arm, respectively. HIV incidence among women with the best adherence was 54 percent lower than placebo, indicating that effectiveness was linked to adherence. Furthermore, the study found tenofovir safe. Despite the small sample size, this study provided “proof of concept” for tenofovir microbicide prophylaxis. More studies are needed to corroborate these findings.

Cited preferences for “dry” sex among certain populations in sub-Saharan Africa raise concerns about the acceptability of vaginal gel microbicides. To identify whether such use would be problematic, 118 in-depth interviews and 15 focus group discussions with women participating in a microbicide gel trial in Kwazulu-Natal and their partners collected detailed information on intravaginal insertions. Unexpectedly, 49 of 63 interviewed women and 4 of 8 men said the microbicide enhanced their sexual pleasure; the remainder reported no effect of the microbicide on their sexual experience. Participants stated that the gel increased sexual pleasure by making sex “hot,” “tight,” “smooth,” and “dry.” Women also reported enjoying the lubricating effect of the gel. According to this research, the notion of “dry” sex is not one of complete dryness, just lack of excessive wetness in the vagina. Furthermore, as intravaginal “potions” were commonly used to improve sexual pleasure among this population, a microbicide may be more easily understood in a local context using local terms. The authors conclude that microbicides may be more acceptable for HIV prevention than expected, as previous associations between intravaginal insertions and dry sex were “overstated.”

This document contains the abstracts of all oral presentations and poster sessions given at the 2010 International Microbicides Conference. Organized by conference days, readers can browse through the content, search the document for authors or keywords, or scroll to the author index at the back of the document. The theme of this conference was “Building Bridges to HIV Prevention,” which is reflected in the abstracts.

This study assessed the acceptability of the Duet® cervical barrier together with a gel in 103 primarily married women in peri-urban Zimbabwe. Women were randomized to use the Duet continuously for 14 days, then only use it before having sex; another arm was randomized to the same regimen in reverse sequence. Approximately 90 percent of the women reported adhering to their assigned regimen 80 percent of the time. Overall, acceptability was high. Half of the participants preferred using the barrier during sex, 39 percent preferred continuous use, and the remainder reported no preference. The most positive attribute women assigned Duet was “normal/natural sex.” No serious adverse events were found among the study participants. Of note, 5 percent of women in both arms reported unspecified “fear” related to use. This study was small and only followed women for one month. Longer-term use may affect acceptability; adverse events may also differ with long-term use.

Microbicides in the Prevention of HIV Infection: Current Status and Future Directions

Nuttall, J. Drugs (2010), Vol. 70 No. 10, pp. 1231–1243.

An in-depth review of the history of microbicide development for HIV prevention, this article also presents new microbicides under development. These include antiretroviral drugs and drug combinations that can be administered in different ways, including daily delivery and sustained delivery mechanisms. In addition to specifically targeted HIV replication, new product options related to timing of use can potentially improve product effectiveness. Potential new microbicides, however, come with concerns about toxicity and resistance. Additional challenges to microbicide development, such as need to remain stable in a tropical environment, are also addressed in the article. The author details concerns and further challenges to introducing a microbicide widely in a population, including knowing its safety profile among pregnant women or women who want to become pregnant. Despite recent encouraging news about microbicides, the road to their widespread and effective use for HIV prevention remains long.

Describing their in vitro and ex vivo testing of tenofovir, the authors make the case that preclinical testing of microbicide products has advanced tremendously over the last decade. Previous microbicides shown to cause cell irritation were not tested so extensively prior to their use in phase II and phase III trials. This study used human ectocervical and colorectal tissue to understand the effects of tenofovir gel on such tissue. In vitro tests found viscosity similar to other commonly-used vaginal and rectal lubricants, constant tenofovir release rates in the gel, and penetration of the drug into mucosal tissue, albeit at varying rates. The gel had no negative effect on vaginal flora, even in the presence of four different bacteria, including gonorrhea. Furthermore, tenofovir reduced the presence of HIV in the tests. Thus the authors conclude that tenofovir is effective and may be a viable candidate for pre-exposure prophylaxis in humans.

This press release from the Microbicides Development Program (MDP) summarizes the outcome of the MDP 301 trial that tested the effectiveness of PRO 2000 vaginal microbicide gel against placebo for HIV prevention. Disappointingly, data from over 9,000 women in four countries in Africa over 12 months (24 months in Uganda) found no difference in HIV acquisition rates between microbicide and placebo users. HIV incidence was 4.5 per 100 women years in the PRO 2000 group and 4.3 per 100 in the placebo group. Readers can find links to PDF files after the press release with additional information, including questions and answers about the trial, the results, quick facts, a technical fact sheet, and “Women’s Voices,” a sheet with study participants’ perspectives of the trial.

Safety and efficacy studies are needed before microbicides can be tested in humans. This trial assessed how well tenofovir (TVF) vaginal gel or TVF with emtricitabine (FTC) protected 17 macaques from simian HIV (SIV) infection over a period of 20 weeks. The gel was administered twice weekly; simian-human immunodeficiency virus was administered 30 minutes after the gel. Five of six macaques in the placebo arm and both in the control arm (no intervention) became infected with SIV in an average of 2.5 weeks. None of the six macaques assigned active gel (TVF alone or TVF+FTC) became infected over 20 weeks (40 total SIV exposures). Furthermore, there was no evidence of damage to vaginal mucosa with use of either active microbicide. Despite study limitations, the authors conclude that this study suggests TFV gel can be used before intercourse to protect women from SIV without the need for daily use.

Researchers undertook this pilot study to identify ways to maximize adherence to diaphragms and microbicide gel ahead of a future study on microbicide effectiveness. Nearly 200 female sex workers (FSWs) in four cities in Madagascar were randomized into four groups: the gel microbicide Acidform plus diaphragm; placebo gel plus diaphragm; placebo gel; and Acidform gel. These were collapsed into two arms for data analysis: diaphragm plus gel or gel alone. Weekly follow-up meetings over one month collected information on product use and sexual practices with clients and regular partners. A statistically significant difference was found in adherence among women randomized to diaphragms (43 percent at first follow-up and 67 percent at last follow-up) compared to gel-only users (28 percent at first follow-up and 45 percent at last follow-up). Compliance improved over time in both groups. The authors believe this was due to the product protocol: diaphragm insertion was a daily event independent of sex, while the gel was to be used prior to coitus. Study findings will help develop counseling messages for future microbicides studies, helping women understand that discreet use is possible, but also indicating that some women choose to disclose product use to their partners.

HIV transmission during anal sex is higher than with vaginal sex due to physiologic factors. As such, a microbicide that can be safely used with anal intercourse could benefit heterosexual and homosexual couples alike. This study in 16 macaques assessed the effectiveness of a rectal tenofovir microbicide gel in preventing simian HIV (SIV) when administered up to two hours before and 15 minutes after rectal exposure to SIV. All placebo-arm macaques and two of the three receiving tenofovir after HIV exposure became infected with SIV. Eight of nine macaques assigned tenofovir before HIV exposure were completely or partially protected from SIV. The higher the tenofovir concentration in the blood 15 minutes after its administration, the greater the protection against SIV. Activated T-cells were found in the blood of the macaques protected from SIV, indicating that such exposure may be able to “prime and/or boost immune responses elicited with experimental vaccines.” This study’s results suggest that tenofovir rectal microbicide gel may have promise in humans.

This review of 118 studies—45 clinical and 73 preclinical—from a biomedical perspective assesses the state of microbicide development for HIV prevention. The authors first discuss the sexual HIV transmission pathways and how microbicides are being developed to address them. The different types of microbicides (e.g., viral entry inhibitors) are described, along with the current state of research for each type. The authors also discuss epidemiological and biological issues that make microbicide research challenging. Epidemiologic issues include HIV incidence, study populations, and discreet use of microbicides. Among biologic challenges are developing combination microbicides when each component must be first tested individually. The authors conclude that while the development of effective microbicides is difficult, the potential benefits are so great that they greatly outweigh any known risks—and possibly unforeseen risks as well.

Over 2,100 women in Lagos and Ibadan, Nigeria participated in a double-blind, randomized, placebo-controlled trial to assess the effectiveness of SAVVY vaginal microbicide gel in preventing HIV transmission. Participants filled out monthly questionnaires on sexual behavior, condom use, gel use, and any medical problems and were given 60 condoms and 60 vials of gel every month. Condom and gel use decreased over the 12-month study period over time, but was generally high. Adverse event rates were the same in both study arms, with no significant difference in chlamydia, bacterial vaginosis, candidiasis, or trichomoniasis rates between arms at the six-month follow-up visit. The study ended early due to lack of power to detect a statistically significant difference in HIV rates between study arms. While the ratio of HIV infections was higher in the SAVVY arm than placebo, the difference was not statistically significant. However, because of the study’s low power, the results cannot conclusively support that SAVVY does not increase risk of HIV infection. This study highlights research challenges in measuring microbicide effectiveness.

This article describes the progress made in recent years to develop microbicides—gels, suppositories, or other topical formulations that prevent HIV—for rectal use. The design and results of early vaginal microbicide trials informed the research direction for evaluating potential rectal microbicide candidates, as did early acceptability studies among men who have sex with men, who are highly vulnerable to HIV because of the common practice of unprotected receptive anal intercourse. Most rectal microbicides in the pipeline have reached only the preclinical study stage. Only two products—UC781, a non-nucleoside reverse transcriptase inhibitor, and tenofovir, a nucleotide inhibitor—have reached the clinical study stage, although L’644, a promising fusion inhibitor, is now also being evaluated. Qualitative and clinical studies of acceptability for different rectal microbicide formulations have found gels to be most acceptable. Rectal safety became the focus of research soon after researchers found that vaginal microbicide candidates were not optimal for rectal use, causing mucosal damage in the rectum; recent research findings show that reducing the glycerin in the formulation may be less harmful. The author describes the preclinical evaluation of four rectal microbicide candidates that have undergone Phase I trials: HIVNET-008 (N9 gel), RMP-01 (UC781 gel), RMP-02/MTN-006 (tenofovir gel), and MTN-007 (tenofovir gel with reduced glycerin). In his conclusion, the author suggests that Phase I studies on rectal microbicides will continue to produce important data on safety, acceptability, and pharmacokinetics that will contribute to early product development.

The authors of this systematic review found that by the end of 2011, nine randomized controlled trials (RCTs) enrolling 31,941 sexually active women in 11 countries, with HIV incidence as the primary outcome, had demonstrated limited evidence that vaginal microbicides reduce acquisition of HIV and herpes simplex virus (HSV-2) infection in women. As a result, the authors do not recommend topical microbicides for HIV or STI prevention, but do suggest that development of new microbicides continue. Of the nine RCTs, the authors found that CAPRISA 004, a small proof-of-concept RCT enrolling 889 women, demonstrated that tenofovir—a nucleotide reverse transcriptase inhibitor—may reduce the risk of acquiring HIV and HSV-2. The authors are currently awaiting data from a second tenofovir trial enrolling 5,000 women, which was stopped early due to futility of results demonstrating a protective effect. According to the authors, other types of topical microbicides did not demonstrate a reduction in the risk of acquiring HIV or sexually transmitted infections (STIs), and none of the trials demonstrated that microbicides reduce the acquisition of other STIs, including gonorrhea, syphilis, genital warts, trichomoniasis, or human papillomavirus infection. The authors stress that if further studies demonstrate the effectiveness of tenofovir-based microbicides, efforts must be made to achieve rapid regulatory approval and create appropriate mechanisms for distribution.

The excitement among the international microbicide development community resulting from the positive one-percent tenofovir trial results has given way to a sense of urgency—urgency to rapidly make available an approved, affordable, and easily obtainable microbicide to the world’s women. This meeting brought together researchers, advocates, program implementers, funders, and regulatory agencies to identify concrete actions these actors can take to bring the one-percent tenofovir microbicide to women as quickly as possible. The report reviews discussions taking place during the meeting and presents the decisions made on what confirmatory studies should move forward, who will lead licensure efforts, and other necessary steps. Appendix 2 includes a summary of completed, ongoing, and planned microbicide clinical studies of one-percent tenofovir gel.

Ten married couples in Pune, India, participating in a microbicide clinical trial formed the basis for separate in-depth interviews on spousal communication about sex and sexual matters. Most couples reported nonverbal communication or using code words about sex because they often lived with extended families and usually did not sleep alone. Lack of knowledge about sex and sexuality as well as a lack of privacy limited couple communication. Five couples reported communicating about sex as a “side effect” of being in the clinical trial, despite this not being a part of the intervention. In addition to initiating discussions about HIV, these couples also reported appreciating having a space to talk about sex openly in the interviews. Many couples reported that their improved communication had a positive effect on their overall relationship. While this sample is not representative of Indian couples at large, it does indicate starting a dialogue about sex and sexuality encourages more communication about sex among the couple. Such communication is the crucial first step to reducing one’s risk of HIV.

This report of a consultation attempts to clarify 2007 Joint U.N. Programme on HIV/AIDS and World Health Organization guidance on prevention standards in HIV prevention trials. As new research and evidence emerge about what is effective in preventing HIV, studies and trials will have to include these new technologies as standards of care in their work. Thus this report tries to translate ethical guidance into day-to-day research practice, taking into account that the guidelines were intentionally written to be flexible, given vastly differing circumstances, epidemics, and access to care. This report reviews the evidence on “what works,” realities of implementing prevention trials, and the current standard of care for HIV prevention trials. It also presents points of agreement and disagreement among the participants of the consultation, and identifies needs for additional guidelines and criteria for those undertaking HIV prevention research.

This poster presentation explores women’s attitudes to discreet use (use without their partner’s knowledge) of a cervical barrier together with a microbicide. Among 83 married women in the trial, all had told their primary male partners about their use of the method by the end of the four-week trial. Focus group discussions among 41 women, however, indicated that they would use the barrier/microbicide without telling their primary partner if necessary. The rationale for telling their partners was to facilitate communication between the couple and avoid any problems should the use be found out. When probed about the reasons for discreet use, however, the women stated that they would indeed use a method that would protect them from HIV, given that most men are likely to have partners on the side. They felt it was important to safeguard their health, and therefore, that of their family. Telling partners about microbicide use may be a way to enlist male support for women’s protection from HIV. Furthermore, the trial demonstrated to women that the method can indeed be used without their partners knowing about it.

This brief focuses on the potential of microbicides to integrate HIV prevention and the empowerment of sub-Saharan African women. The authors argue that empowering women can help offset the social, cultural, and economic factors that place women at disproportionate risk of acquiring HIV. Microbicides, they posit, can help become tools of women’s empowerment if women’s rights are at the forefront of microbicide development, strategy, and roll-out. The authors present four issues that must be addressed if microbicides are to become a tool for both HIV prevention and women’s empowerment: effectiveness, availability, stigma, and partner communication.

Full and active engagement of the civil society in microbicide development can benefit everyone from researchers to the women who stand to benefit from microbicide use. A small working group identified seven priority gaps in microbicide research and development that civil society organizations could fill. The gaps were then broken down into concrete, actionable steps, resulting in 55 action steps for civil society, government/policymakers, researchers, and funders/sponsors. These “interlocking” steps show how each group’s work complements and enhances the other groups’ efforts. The report also highlights the importance of having an enabling environment to advance microbicide research, and what can be done to create such an environment.

Identifying Optimal Strategies for Microbicide Distribution in India and South Africa: Modelling and Cost-Effectiveness Analyses

Watts, C., Foss, A., Kumaranayake, L., et al. International Partnership for Microbicides and London School of Hygiene and Tropical Medicine, (2008).

Developing an effective microbicide is only the first step in saving women’s lives. To truly be effective for HIV prevention, microbicides must be made widely available—entailing licensing, regulatory, and service delivery considerations—and be affordable and acceptable to all potential users. Researchers considered these factors when modeling how long it would take to see widespread microbicide use in southern India and South Africa. Stakeholder meetings reviewed women’s reproductive health product introduction experiences and identified other key inputs for the models such as approval time and target audience penetration. Fully 120 scenarios were modeled and considered for India, while 156 were considered for South Africa. This paper describes the process and scenarios and juxtaposes the 10 most effective scenarios with the cost-effectiveness of each. While potential exists for microbicides to become another tool for HIV prevention, their widespread use can take significant time and resources.

Nearly 900 men who have sex with men in San Francisco participated in this random-digit dialing telephone survey about microbicides and Nonoxynol-9 (N-9). Nearly 4 of every 10 respondents sexually active in the last year reported unprotected receptive anal intercourse, while 45 percent reported unprotected insertive anal intercourse. Only 39 percent of the sample knew that N-9 could injure rectal tissue, thus potentially creating an entryway for HIV. N-9 use among these men in the last year was 26 percent. Men reporting recent unprotected anal intercourse were more likely to use N-9, which may indicate risk compensation or that these men are seeking alternatives to condom use for HIV prevention. Only 7 percent believed that N-9 could prevent HIV transmission. Although an effective microbicide was not on the market, 59 percent of the sample understood that a microbicide could reduce the risk of HIV. Interestingly, compared to uninfected men, those with HIV were more willing to use a microbicide that was less effective at preventing HIV than condoms.

Risk compensation theory posits that individuals will maintain a constant level of risk over time. As risk reduction behaviors are implemented (e.g., condom use), people will adjust other risky behaviors upward to compensate for the safety behaviors (e.g., have more sex partners), thus maintaining the same level of risk as before. This literature review examined whether study participants reported risk compensation behaviors when participating in trials of HIV vaccines, microbicides, male circumcision, and antiretroviral therapy (ART). Evidence was available for ART, HIV vaccines, and circumcision. Although limited, the few studies focusing on risk compensation among HIV vaccine trial participants found evidence of increased risky behaviors. A meta-analysis of highly active ART (HAART) also found more unprotected sex among HAART users who thought that HAART reduced the likelihood of HIV transmission. Similarly, circumcised men had riskier sexual behaviors (more partners and less condom use) compared to men who were not circumcised. The authors conclude that HIV prevention interventions must include risk compensation considerations into their programs.

This video was developed to help with microbicide advocacy efforts, particularly in countries and communities where such research is taking place. It answers basic questions about microbicides (what they are, how they work, how effective they are) as well as addresses HIV prevention and transmission. It also covers essential information about clinical trials. The video is available as a 100-second summary or as the full 20-minute version in English, French, kiSwahili, isiXhosa, and isiZulu.

This webpage contains brief descriptions of the Population Council’s microbicide research projects taking place worldwide, with links to more in-depth information about each study. Older trials also have links to documents containing results, while ongoing trials provide descriptions of the work done to date. The research portfolio includes studies that assess ways to improve adherence to product use, different modes of microbicide delivery such as vaginal rings, and user acceptability research. Some novel approaches include computer-assisted self interviews being used in Malawi, South Africa, Uganda, the United States, Zambia, and Zimbabwe. This technique provides interviewees more privacy and confidentiality than answering aloud in face-to-face interviews.

The study sought to quantitatively and qualitatively explore the acceptability of a vaginal ring (VR) among sexually active women in Tanzania and South Africa. The ring could be used for the delivery of microbicides for HIV prevention if acceptability was high. The VR was provided to 158 women in the randomized trial. The ring had no active ingredient and was, therefore, a placebo. Participants were taught how to insert and remove the VR in the clinic. The women visited the clinic four times throughout the twelve-week trial for an exam and were asked about their comfort levels and experiences with the VR using a questionnaire. Focus group discussions and in-depth interviews were conducted with the women and their male partners, if the women gave the researchers permission. It was found that the majority of the women were able to successfully insert the VR (81 percent), and that retention over the twelve-week study period was high (97 percent). The women reported few concerns or problems about the VR during the study. The most frequently reported concern (20 percent at week 4) was that it would get lost in their body. The three most favorable characteristics of the VR at the 12-week point for the women was that it may be used someday to prevent HIV, does not interfere with sex, and that you can still use a condom with the VR. The three least liked characteristics of the VR were that it may get lost in the body, may come out during sex, and may change the feeling of sex for the partner. The VR was found to be highly acceptable for both the women and their partners in this study.

This informative and engaging online course uses various media to teach people about microbicides, including readings, video clips, animated anatomical and biological graphics, and interactive quizzes. Eight modules cover what microbicides are, how they work, how they are developed, issues related to access and use, and how clinical trials test microbicide effectiveness. Users can take quizzes and tests to assess their knowledge and view videos of advocates answering common microbicide questions. The last module provides an overview of the current microbicide landscape, including mobilizing funding and community support for this method of HIV prevention. (Readers must register to access the full course; registration is free.)

Safety and Effectiveness Study of a Candidate Vaginal Microbicide for Prevention of HIV

Centre for the AIDS Programme of Research in South Africa, Family Health International, United States Agency for International Development, & CONRAD. (2010).

This webpage contains the full study protocol for a clinical trial of tenofovir gel as a vaginal microbicide for preventing HIV. In addition to a detailed description of the study design, population, objectives, and regimens, information on eligibility, principal investigators, study sites, and collaborating institutions is available, including contact information. The page also provides links to publications related to this research and additional information on the study.

As advocates who have been working with members of civil society throughout the world on microbicides, the Global Campaign for Microbicides has extensive experience in communicating about microbicides to multiple audiences. This short brief clearly states seven talking points the organization follows and urges partners to follow. Among the points are the fact that microbicides are not a “magic bullet” and acknowledging that technological tools cannot replace the need for women’s empowerment.

This short brief provides useful and practical information on how to organize a successful community forum on microbicides. Broken down into 10 steps, the following are included: consideration of partners to co-host, deciding on an agenda that the community would find interesting and engaging, logistics, budget, and spreading the word about the event. Readers can find excellent tips on engaging the media and following actionable steps to ensure ample participation from the local community and members of the media alike.

This document argues that in addition to the scientific research taking place on microbicide effectiveness, a parallel path must also take place among the international microbicide community: developing plans for microbicide access and use. Focusing on the five primary dimensions of access—acceptability and use; a supportive policy and social environment; availability; affordability; regulatory approval and licensing—each chapter lays out goals, objectives, and proposed activities that can help ensure that once an appropriate microbicide has been identified, structures are in place to rapidly make it affordable, accessible, and useable.

There is much potential for misunderstanding and controversy surrounding clinical trials. This handbook helps researchers, program managers, and others understand these communication challenges and guides readers on how to best share information with local communities and partners. It includes general communication guidelines, lessons learned from other country experiences, and multiple tools, such as risk assessment tools and sample templates that can sharpen staff skills in accurately answering questions about the research taking place. Sample communication plans as well as tips and techniques on communicating effectively in various fora are also included in the handbook.

The website offers the latest news on the past, present, or ongoing status of biomedical HIV prevention research studies. Readers can review summary tables from various HIV prevention clinical trials, search information on prevention trials, see what is new on the site each month, and review the user’s guide for help in using the site. The site offers information about the following biomedical prevention trials: microbicides, pre-exposure prophylaxis, treatment as prevention, and vaccines.

This webpage provides information on U.S. Agency for International Development (USAID) activities related to microbicides, including the agenda, presentations, and meeting report of the high-level Microbicides Stakeholders Meeting in late 2010. Readers can find information on the agency's financial support for microbicides development, their stance on the results of the Centre for the AIDS Programme of Research in South Africa 004 trial, partnerships for microbicide support and development, as well as current USAID activities on microbicides research and development.

Because microbicides are a relatively new product, little guidance exists on the regulatory requirements needed at different stages of product testing and data necessary for licensure. To address this gap, the World Health Organization held six consultations in Europe, Africa, and Asia from 2002 to 2008. The first consultation drafted the minimal regulatory requirements for microbicide trials and eventual product licensing. Subsequent consultations opened a dialogue among in-country researchers, policymakers, and regulators about microbicide regulatory issues, with an aim to alleviate constraints to microbicide development. This report discusses the role of regulatory authorities in non-clinical and clinical microbicide studies, including safety, effectiveness, epidemiological principals, and pharmacology, as well as issues specific to microbicide use.

This webpage provides an overview of CONRAD's microbicide research activities, starting from some of the first microbicides developed in the 1990s to today's formulations that contain antiretroviral drugs. Readers can click on links to obtain more information on the development process for microbicides, as well as CONRAD's preclinical and clinical microbicide activities. In addition, information is available about their dual-protection microbicides that protect women from pregnancy in addition to sexually transmitted infections and/or HIV.

This webpage provides readers with links to microbicide information, including introductory information to those that may not be familiar with the topic. A microbicide fact sheet is available in English, Spanish, French, Portuguese, and Thai for readers to download and disseminate. Readers can also follow a link to a collection of microbicide resources, including question and answer sheets and summaries of ongoing microbicide clinical trials. Readers can also link to a page that provides breakdown of clinical trials: ongoing trials, trial results, and planned trials.

The Global Campaign for Microbicides promotes the rapid yet ethical development of and widespread access to HIV prevention options, especially for women. The organization collaborates with all sectors, from civil society to industry, and does not support any one product. This website includes information on microbicides, clinical trials, other prevention options such as female condoms and male circumcision, and more. Resources are available in English, French, Spanish, and Russian.

This brief fact sheet clearly explains the biology of microbicides and how microbicides may work to help protect users from HIV, complete with references to selected research articles providing more detailed information. A useful graphic shows how a virus enters by disrupting the vaginal skin cell layers and also depicts how microbicides may be able to stop such disruption, and thus, viral entry.

The International Partnership for Microbicides (IPM) is an organization founded as a product development partnership. Its mission is to speed the development of microbicides and other HIV prevention mechanisms for women in developing countries. Working with partners from academia to biotechnology companies to civil society organizations, IPM has several compounds in development and in various stages of clinical trials. Their website offers information on their work, different HIV prevention products for women, media resources, scientific articles, and other publications about microbicides.

International Rectal Microbicides Advocates is an organization of individuals worldwide working to advance research and development of safe, effective rectal microbicides for men, women, and transgender individuals to use for HIV prevention. Materials that can be accessed on their website include information on the safety of lubricants for anal use, scientific articles, media stories, fact sheets, and more. This highly interactive site includes blogs and subscription to a moderated listserv. Links are available to sister websites for Nigeria and for Latin America and South America.

The Medium Matters: Applicators are Crucial to Success of Microbicides

PATH. (n.d.).

Something as simple as what kind of applicator is used in microbicides can have a significant impact on the product—for example, its cost, usability, and safety. PATH provides an interesting perspective on product development by describing the considerations behind applicator design, their choices between using single-use applicators and multiple-use applicators, and user-testing. Through this description, readers can see the balancing act required to be able to meet women's needs while also making a product safe and affordable. PATH is now working to obtain regulatory approval for microbicide applicators so that they can quickly be made available once a microbicide becomes available.

The biennial International Microbicides Conference, held in April 2012 in Sydney, Australia, focused on HIV prevention technologies, including the use of antiretroviral-based microbicides and pre-exposure prophylaxis (PrEP); adherence in clinical trials; innovative financing; dual prevention technologies; and new methods of preventing rectal transmission of HIV. In the keynote address, Dr. Salim Abdool Karim, co-principal investigator of the CAPRISA 004 trial, discussed implications and lessons learned nearly two years after the trial provided proof of concept for antiretroviral-based microbicides. In the opening plenary, Dr. Connie Celum of the University of Washington discussed the emerging evidence from recent oral and topical tenofovir-based PrEP trials that have demonstrated efficacy ranging from 39 to 75 percent. She emphasized the ongoing challenges of adherence, risk perception, and delivery of PrEP to most-at-risk populations. She urged researchers to continue to explore longer-acting products that are less adherence-dependent. To address the need for rectal microbicides, International Rectal Microbicide Advocates (IRMA) released a strategy document entitled The Map: Ensuring Africa’s Place in Rectal Microbicide Research and Advocacy. Other presenters focused on a variety of topics, including multi-prevention technologies, access to microbicides, and recent findings from PrEP trials. The conference closed with a presentation from Gina Brown, U.S. National Institutes of Health, and Stephen Becker, Bill & Melinda Gates Foundation, who announced that the biennial microbicide conference will be replaced with a biennial global HIV prevention conference focusing on vaccines, microbicides, and oral PrEP.

This website is implemented by John Snow, Inc. This Project is funded by the U.S. Agency for International Development under contract number GHH-I-00-07-00059-00 Task Order No. 01 and the President's Emergency Plan for AIDS Relief (PEPFAR).

The information provided on this web site is not official U.S. Government information and does not represent the views or positions of the U.S. Agency for International Development or the U.S. Government.